Finn T. Jensen

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement.

BACKGROUND The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size. METHODS Forty patients aged 24 to 82 years who survived aortic valve replacement for aortic stenosis with a standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were followed up prospectively with Doppler echocardiography and radionuclide left ventriculography preoperatively and 9 days, 3 months, and 18 months after the operation with assessment of intravascular hemolysis at 18 months. Follow-up to a maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS Left ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to 153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase in left ventricular ejection fraction, peak ejection rate, and peak filling rate; only 18% of the patients had normal left ventricular muscle mass index and only 32% normal ventricular function (normal left ventricular ejection fraction, peak ejection rate, peak filling rate, early filling fraction, and late filling fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak gradient and size of the valve. Peak gradient at 18 months rose with valve orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg). All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two patients with moderate paravalvular leak had the highest serum lactic dehydrogenase levels; 4 patients with trivial leak had higher serum lactic dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels rose with moderate paravalvular leak, impaired ventricular function, and valve orifice diameter. Six patients with trivial or moderate paravalvular leak had a cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22% compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS The peak gradient of the St. Jude aortic valve dropped marginally over the first 18 postoperative months in association with incomplete left ventricular hypertrophy regression and marginal improvement of ventricular function. Mismatch between valve size and ventricular cavity size or patient size and impaired function of a dilated ventricle significantly compromised the performance of the St. Jude valve. Probably explained by platelet destruction or activation, paravalvular leak was related to bleeding and thromboembolic complications.

Fasting in healthy subjects is associated with intrahepatic accumulation of lipids as assessed by 1H-magnetic resonance spectroscopy.

The impact of fasting on IHL (intrahepatic lipid) content in human subjects has not been investigated previously, but results indicate that it may change rapidly in response to metabolic cues. The aim of the present study was to measure IHL content after fasting and to correlate this with circulating lipid intermediates. A total of eight healthy non-obese young males were studied before and after 12 or 36 h of fasting. IHL content was assessed by (1)H-magnetic resonance spectroscopy, and blood samples were drawn after the fasting period. IHL content increased significantly after the 36 h fasting period [median increase 156% (range, 4-252%); P<0.05]. Furthermore, a significant positive correlation between this increase and 3-hydroxybutyrate concentration was detected (P=0.03). No significant change in IHL content was demonstrated after the 12 h fasting period. The baseline median inter-individual variation in IHLs was 0.51% (range, 0.25-0.72%). The coefficient of variation of IHL measurements was 11.6%; 25-30% of the variation was of analytical origin and the remaining 70-75% was attributed to repositioning. In conclusion, IHL content increases in healthy male subjects during fasting, which demonstrates that nutritional status should be accounted for when assessing IHLs in clinical studies. Moreover, the increase in IHLs was positively correlated with the concentration of 3-hydroxybutyrate.

Ischemia in Wound Healing I: Design of a Flap Model—Changes in Blood Flow

A standardized ischemic, H-shaped, double flap model in rats was developed for investigating the influence of different factors that could potentially increase flap survival. The blood flow was measured in the flaps as well as in normal healing incisional wounds on day -1 (intact skin) and on days 1, 4, 8, and 16 by the xenon-133 (133Xe) clearance technique. The flow in normal healing incisional wounds remained the same as the flow in intact skin. The flow in the flaps, however, initially decreased to ischemic levels, but afterwards gradually increased to that of normal healing incisional wounds and intact skin. Further, the cutaneous blood flow in both the cranially and the caudally based ischemic dorsal flap was independent of the width of the flap.

Delayed Primary Closure. Blood-Flow in Healing Rat Skin Incisions

In an earlier study delayed primary closure (DPC) wounds were shown to develop higher biomechanical strength than primary closure (PC) wounds. In order to elucidate the underlying mechanism, local clearance of 133Xenon and thermography studies were undertaken. A paired comparison design with deposits of 133Xenon injected in the wound margins 3 and 4 days postoperatively, and directly into the wound tissue 10, 20 and 60 days postoperatively was used. Very pronounced differences, with higher blood-flows for DPC wounds, were found in the early measurements. In the later measurements there were significant but less obvious differences. With thermography no differences could be detected. It is concluded that DPC wound have a higher blood-flow, especially in the initial wound healing phase. This supports the hypothesis that an increased blood-flowing during early wound healing is beneficial for the development of mechanical strength in the maturing normal scar.

Late Cardiac Deaths After Isolated Valve Replacement for Aortic Stenosis. Relation to Impaired Left Ventricular Diastolic Performance

Sixty-three patients took part in a follow-up study ten to seventeen years after valve replacement for aortic stenosis. Data obtained were used to predict cardiac deaths (n = 14) occurring in the following three-year period. The degree of residual left ventricular (LV) hypertrophy correl ated inversely with indices for LV sys tolic and diastolic performance (radionuclide cardiography). A logis tic regression (LR) model had a posi tive predictive value for cardiac deaths of 100% (10/10) with 8% (4/53) false negatives. Evaluating LV performance indices exclusively, LR analysis showed that only peak filling rate had independent predictive value. Subnormal and normal LV ejection fractions were associated with equal three-year cardiac death rates (29%). Depressed LV function was re lated to residual hypertrophy. Im paired diastolic performance was the prime predictor of cardiac deaths.

Reliability of three computer methods in the analysis of ECG-gated radionuclide left ventriculography: interrecording, interobserver and intraobserver variability.

Three different computer methods for analysis of systolic and diastolic left ventricular function (ejection fraction, peak ejection rate, time to peak ejection rate, peak filling rate, time to peak filling rate, duration of fast filling phase, and fast filling fraction) as derived from ECG-gated radionuclide cardiography were compared in 30 patients with various diseases. The patients had two gam ma camera recordings of the left ventricle performed immediately following one another during radionuclide (99mTc) equilibrium (3 x 106 counts, 16 frames/cy cle, 64 x 64 pixels). Mean ECG R-R interval of the patients remained unchanged from first to second recording. The three computer methods were: (1) end-diastolic (ED) region of interest (ROI) analysis based on manually defined ED-ROI; (2) multi (M) ROI, manually defined ROI for each frame; and (3) semiautomatic (SA) ROI, ROI for each frame defined by an SA edge detection technique. With the 16 frame points as nodes, a 160-point time-activity curve was constructed for each of the three methods by use of a spline function. A tailored multiway analysis of variance showed that the M-ROI method had the highest interindividu al range of values of the function parameters and the smallest interrecording, interobserver, and intraobserver variabilities. In theory this implies a better di agnostic sensitivity and specificity for the M-ROI method as compared with the other two methods.

Aortic regurgitation after surgical relief of subvalvular membranous stenosis (a long-term follow-up study)

A postoperative follow-up study of 21 cases of discrete membranous subvalvular aortic stenosis is presented. The age at operation was 6-47 (mean 16) years, and the follow-up time 0.6-16 (mean 6.7) years. Preoperatively most patients were in NYHA function class II or III and had high peak systolic pressure gradient, left ventricular hypertrophy and/or cardiothoracic index greater than 0.50. At follow-up all but six patients were in NYHA class I, the Doppler-estimated peak systolic gradient was 0-36 (mean 18) mmHg, the cardiothoracic index unchanged and the mean left ventricular hypertrophy score had declined from 4.3 to 2.3. Of 13 patients without aortic regurgitation preoperatively, eight had regurgitation at follow-up (group I) and five did not (group II). The interval to follow-up was significantly longer and the preoperative peak systolic gradient was greater in group I than in group II. Aortic regurgitation may develop even after surgical relief of discrete membranous subvalvular aortic stenosis, possibly associated with high preoperative pressure gradient and time from operation. Regular postoperative Doppler echocardiography is therefore recommended.

Hemodynamic function of the standard St. Jude bileaflet disc valve has no clinical impact 10 years after aortic valve replacement

Objectives: Size mismatch and impaired left ventricular function have been shown to determine the hemodynamic function of the standard St. Jude bileaflet disc valve early after aortic valve replacement (AVR). We aimed to analyse St. Jude valve hemodynamic function and its clinical impact in the survivors of a prospective series 10 years after AVR for aortic stenosis. Design: Forty-three survivors aged 32–90 years from a prospective series attended a follow-up study with Doppler echo and radionuclide cardiography 10 years after AVR for aortic stenosis. Six patients with significant left sided valve regurgitation were excluded from further analysis: they had significantly lower St. Jude valve gradient and left ventricular ejection fraction (LVEF) and larger mass index (LVMi) than 37 without. Results: In the 37 patients without left sided valve regurgitation peak and mean gradients were inversely related to St. Jude valve geometric orifice area (GOA) indexed for either body surface area or left ventricular end-diastolic dimension (LVEDD). The gradients correlated directly with LVEDD but not with LVEF or LVMi. Eleven patients with hypertension had higher peak gradients (31±13 versus 22±8 mmHg, p < 0.05), lower LVEF, and higher LVEDD and LVMi than 26 without. Peak gradient was greater than 35 mmHg in five hypertensive patients with normal LVEF but lesser than 30 mmHg in six with impaired LVEF. Supranormal LVEF and severe size mismatch identified the remaining patients (N = 3) with peak gradient above 35 mmHg. In a multilinear regression analysis GOA indexed for LVEDD, hypertension, and LVEF were independently related to peak gradient. Conclusion: High gradients of the standard St. Jude bileaflet disc valve 10 years after AVR was primarily related to systemic hypertension and mismatch between valve and left ventricular cavity size. Hypertension and left sided valve regurgitation, but not St. Jude valve gradient or size mismatch, were the dominant determinants of left ventricular hypertrophy and impaired function.